Interferons and defensins are antimicrobial peptides that can also induce anti-tumor immunity. By analyzing the copy number profiles of 10759 patients across 31 cancer types, we found the homozygous deletions of interferon and defensin genes are prevailing in most human cancers, and that patients with these homozygous deletions exhibited significant reduced overall survival or disease-free survival. We further demonstrated that the homozygous deletion of interferon and defensin genes significantly impacted the expression of genes regulated by tumor necrosis factor (TNF) and IFNγ;. Our findings suggested a novel immune escape mechanism that disrupts the tumor cells′ ability to be recognized, and have implications for personalized immunotherapy.

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